# Illuminating the understudied druggable kinome through human phenotypes and model organisms

> **NIH NIH R21** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2020 · $218,750

## Abstract

PROJECT SUMMARY
Despite the widely recognized importance of kinases in human biology, a significant portion of the human
kinome remains poorly characterized. A systematic means of identifying connections between understudied
kinases and human physiology could have a transformative effect on human health. One approach is to
leverage emerging genomic datasets and mine for associations between specific gene sets and diseases or
clinical traits. However, the mechanisms by which variants contribute to the disease process are often unclear,
especially in the case of understudied genes. Therefore, integration of complementary methods is required to
frame these genes into biochemical pathways and to begin to understand the mechanisms by which they
contribute to human physiology.
To bridge this gap, we have integrated genetic information with blood levels of metabolites and proteins
(~5,000 analytes) to begin to establish the genetic architecture of the human metabolome and proteome. As
highlighted in the present proposal, our compendium of gene-analyte associations can also be leveraged for
focused interrogations of specific gene sets to create biochemical signatures of metabolites or proteins
“downstream” of common or rare genetic variants. In this proposal, we will generate biochemical signatures of
genetic variation in the understudied kinases (Aim 1). Theses biochemical signatures will highlight potential
new metabolic pathways regulated by kinase biology that can then be validated and studied by genetic
manipulation in model systems. In Aim 2, we will use deep phenotyping studies in model organisms to
illuminate the biological underpinnings of gene-analyte associations. Further, based on recent proof-of-concept
findings, we will test the specific hypothesis that the poorly characterized kinase, CAMK1D, modulates
triglyceride metabolism in vivo.
Successful completion of these aims will provide opportunities to understand the biological functions of
understudied kinases and will provide novel mechanistic insights into the biology they regulate. Further, this
proposal will provide a strong foundation in the application of emerging “multi-omics” approaches to a new
investigator and will lay the groundwork for a subsequent R01 application to use this pipeline to study a range
of understudied genes.

## Key facts

- **NIH application ID:** 9999647
- **Project number:** 5R21HG010392-02
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Anjali Nath
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $218,750
- **Award type:** 5
- **Project period:** 2019-09-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999647

## Citation

> US National Institutes of Health, RePORTER application 9999647, Illuminating the understudied druggable kinome through human phenotypes and model organisms (5R21HG010392-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9999647. Licensed CC0.

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